17,20-dimethyl-18-norpregnenes



United States Patent 3,192,238 17,20-DIMETHYL-18-NORPREGNENES Leslie A. Freiberg, Waukegan, 111., assignor to Abbott Laboratories, North Chicago, Ill., a corporation of Illinois No Drawing. Filed Sept. 9, 1963, Ser. No. 307,323 9 Claims. (CI. 260-397.45)

The present invention is directed to new steroids and a method for their preparation. More particularly, this invention is concerned with the manufacture of substituted 17,20dimethyl-18-norpregn-13-enes.

The compounds embraced by the present invention are those of the general formula These compounds are useful as hormonally active compounds; in particular, they have androgenic activity in warm-blooded animals. Furthermore, these compounds can be used for the preparation of other steroids such as those esterified in the 3,6- and/or 16a-position with lower fatty acids which are also hormonally active.

In a general embodiment, compounds of the present invention are made by rearranging a compound of the formula wherein R is a oxo, a hydroxy or an acyloxy group, in the presence of boron trifluoride etherate in an inert, anhydrous organic solvent at a temperature between 0 and 36 C. The term inert is used herein to express that the solvent does not react with either the starting materials or the expected product. Examples of such inert solvents are benzene, n-pentane, diethyl ether, tetrahydrofurane, cyclohexane, and the like.

To better understand the process for preparing the compounds of the present invention, reference is made to the following examples which, however, are not means to limit the invention in any way.

3,192,238 Patented June 29, 1965 use EXAMPLE I 35 acetoxy 1713,20 dimethyl I8 nor 17a pregn- 5,13-diene-16a,20-di0l To a solution of 2.85 grams of 3B-acetoxy-l6a,17uepoxy-20-methyl-5-pregnen-20ol (described by W. Cole et al. in J. Org. Chem., volume 19, page 131, of 1953) in 125 ml. of diethyl ether, is added 1.0 ml. of freshly distilled borin trifiuride etherate. The mixture is swirled and allowed to stand for 20 minutes at 25 C. whereupon ml. of water containing 2.0 grams of potassium carbonate is added. After shaking the mixture, the ether phase is isolated, washed with water, dried with anhydrous magnesium sulfate, and the ether is distilled. The crude product, weighing 2,72 grams, is taken up in 10 ml. of benzene and chromatographed on 100 grams of neutral activity III alumina. The material eluted with benzene containing from 1% to 10% diethyl ether is crystallized from petroleum ether (fraction boiling at 60-68 C.) to give 0.50 gram of 3 8-acetoxy-17fl,20 diemthyl 18 nor 17cc pregn 5,13 diene 16a,20- diol melting at 148150 C. The analytical data of 74.29% C and 9.25% H is in agreement with the values calculated for the compound with empirical formula 24 as 4- When in the above process the material is taken up in a small amount of ether prior to the chromatographic separation and diluted with 10-20 volumes of petroleum ether (B.P. 60-68), an oil separates. The solution is decanted and concentrated and the concentrate is used for the chromatogram which then produces a much cleaner separation.

EXAMPLE 2 17,20 dimethyl 18 nor 17o: pregn 5,13 diene- 3 5,1 6 a,20iri0l A solution of 0.34 gram of 3;8acetoxy-17fl,20-dimethyl-l8-nor-17upregn-5,13-diene-l6m,20-diol and 0.37 gram of potassium carbonate in 17 ml. of 88% aqueous methanol is refluxed for 4 hours. The material is crystallized by the addition of 15 ml. of water, filtered, and recrystallized from toluene to give 0.16 gram of 1713,20- dimethyl-l8-nor-l7a-pregn 5,13 diene 3fl,16a,20 triol melting at 20003 C. The analytical data of 76.64% C and 9.84% H agrees with the calculated values for the compound with empirical formula C H O From the above 1713,20 dimethyl-l8-nor-l7a-pregn- 5,l3-diene-318,l6a,20-triol, the above shown modifications of the A/B rings can easily be accomplished. Thus, for example, 17,8,20 dimethyl-l8-nor-17a-pregn-4,13-diene- 16,20-diol-3-one is obtained by oxidation of the hydroxy group in the 3-position by known methods, and the corresponding 4- or S-saturated compounds, e.g., 175,20- dimethyl-lS-nor-17u-pregn-13-ene-3,8,l6a,20-triol 3B-acetoxy-l7fl,20-dimethyl-18-nor-17a-pregn 13 ene 1601,20- diol, and 1713,20 dimethyl-l8-nor-17a-pregn 13 ene- 16a,20-diol 3-one are accessible by hydrogenation of the double bond in the precursors named above (compounds of Examples 1 and 2) and/or oxidation of the 3 alcohol function. The hydrogenation is best carried out with gaseous hydrogen in the presence of a platinum catalyst until 1 mole of hydrogen is absorbed.

EXAMPLE 3 319,16 djqgetoxy 17 9,20 dimthyl 18 nor 17apregn-5,13-diene-20-0l A mixture of 48.1 mg. of 3fi-acetoxy-176,20-dimethyl- 18-nor-17a-pregn-5,13-diene-163,20-diol, 1.2 ml. of acetic anhydride and 2.3 ml. of pyridine is allowed to stand overnight at room temperature. A small amount of ice is added to decompose excess acetic anhydride. Addi- 3 tionai water is added, and the 3/8,16a-diacetoxy-17B,20- dimethyl-18-nor-17a-pregn5,13-diene-20 ol crystallizes. It melts at 125-26 C. and the analytical data of 72.50% C and 8.89% H confirm the values of the compound with empirical formula C H O Others may practice the invention in any of the numerous ways which will be suggested to one skilled in the art by the present disclosure. All such practice of the invention is considered a part thereof provided it falls within the scope of the appended claims.

I claim:

1. A compound of the formula.

CII;

OH cH;

wherein the A/B rings have a partial structure selected from the group consisting of and 4. 175,20 dimethyl 18 nor 17a pregn 4,13- diene-16a,20-diol-3-one.

5. 175,20 dimethyl 18 nor 17oz pregn 13 ene- 3B,16a,20-triol.

6. 3B acetoxy 176,20 dimethyl 18 nor cprcgn-13-ene-16a,20diol.

7. 173,20 dimethyl 18 nor 17oz pregn 13 ene- 16a,20-diOl-3-O1'l.

8. 313,16a diacetoxy 175,20 dimethyl 18 nor- 17a-pregn-5,13-diene-20-ol.

9. The process of rearranging a compound ofthe formula wherein R is selected from the group consisting of hydroxy, 0x0 and acyloxy, with boron trifiuoride etherate at a temperature between 0 and 36 C. in the presence of an inert, anhydrous, organic solvent.

References Cited by the Examiner Bowers et 211.: Tetrahedron, vol. 8, 1960, pp. 116-125. Collins: J. Chem. Soc., 1959, pp. 3919-3928.

LEWIS GOTTS, Primary Examiner. 

1. A COMPOUND OF THE FORMULA 